Cyclin D3 immunohistochemical expression was investigated in normal, reactive, and neoplastic human embryonal and adult tissues. In the fetus,
cyclin D3 was expressed in selected developmental phases of a limited number of cell systems. In normal adult tissues,
cyclin D3 showed two patterns of distribution: in lymphoid tissues it was expressed in proliferative compartments, while in most other tissues it was expressed by terminally differentiated/quiescent cells. This dual role in proliferation and differentiation was partially conserved in
neoplasms. In non-Hodgkin
lymphomas,
cyclin D3 immunolabelling was correlated with proliferative activity and progression; a significant exception was seen in
cyclin D1-positive
mantle cell lymphomas, which were
cyclin D-negative. Benign endocrine tumours were frequently strongly
cyclin D3-positive, while high-grade (small cell) neuroendocrine
carcinomas were always negative. In most other
epithelial neoplasms,
cyclin D3 immunostaining was heterogeneous. In
breast carcinomas, no relationship was seen between ER status and MIB1 labelling;
cyclins D3 and D1 were frequently expressed in the same tumour, while occasional tumours showed an inverse quantitative relationship between
cyclins D1 and D3, and rare tumours were negative for both. In
soft tissue neoplasms,
cyclin D3 was consistently expressed in some tumours, such as stromal tumours of the gastrointestinal tract and
embryonal rhabdomyosarcomas. Our data suggest that
cyclin D3 has a dual role in proliferation and differentiation in normal tissues and in some neoplastic conditions; that the
cyclin D3 expression pattern is different from
cyclin D1, suggesting non-redundant functions; that
cyclin D3 expression is strong in endocrine cells secreting
steroid hormones, and in their neoplastic counterparts; and that
cyclin D3 deregulation may be of pathogenetic relevance in lymphomagenesis and could be diagnostically useful.